Inhibition of Epithelial-mesenchymal Transition in Response to Treatment with Metformin and Y27632 in Breast Cancer Cell Lines

Anticancer Agents Med Chem. 2017;17(8):1113-1125. doi: 10.2174/1871520617666170102153954.

Abstract

Background: ROCK-1 expression is associated with the malignant character of tumors, while inhibiting this molecule results in a significant suppression of tumor metastasis. Likewise, transforming growth factor beta (TGF-β) is associated with this malignancy by having the ability to induce epithelial-mesenchymal transition (EMT). Metformin, a drug used in the treatment of diabetes, has previously been shown to inhibit EMT in breast cancer cells.

Objective: The aim of this study is to evaluate the TGF-β1 action model for induction of EMT and the action of metformin and ROCK-1 inhibitor (Y27632) in EMT process in breast cancer cell lines.

Method: MCF-7 and MDA-MB-231 cell lines were treated with metformin and Y27632, after induction of EMT by TGF-β1, to examine the effects on cell migration as well as the protein expression of the ROCK-1 markers, vimentin, E-cadherin, CD44 and CD24 by immunocitochemistry.

Results: There was a lower protein expression of ROCK-1, vimentin, CD44 and CD24 in both cell lines after treatment with metformin and Y27632. In MDA-MB-231 cells, E-cadherin expression was increased in all treatment groups. Treatment of MDA-MB-231 cell line with metformin and Y27632 significantly reduced the invasion of these cells.

Conclusion: This study confirms the benefits of metformin and Y27632 as potential therapeutic agents in mammary tumors, by blocking EMT process and metastatic potential.

Keywords: Breast cancer; EMT; ROCK1; TGF-β; anticarcinogenic agents; metformin.

MeSH terms

  • Amides / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • MCF-7 Cells
  • Metformin / pharmacology*
  • Molecular Structure
  • Pyridines / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • rho-Associated Kinases / antagonists & inhibitors
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • Amides
  • Antineoplastic Agents
  • Pyridines
  • Y 27632
  • Metformin
  • ROCK1 protein, human
  • rho-Associated Kinases